Alessandro Pizzocaro

U.O. Urologia, Servizio di Andrologia Istituto Clinico Humanitas, Rozzano (MI)

Segretario Regionale SIAMS per la Lombardia

Bari 7-10 Novembre

Bari 7-10 Novembre

Key points

•  Prevalence of Testosterone Deficiency (TD) increases with age in particular in pts with metabolic syndrome (about 50%) and sexual dysfunction

•  Low Testosterone levels are associated with reduced longevity and quality of life: •  increase of fatal cardiovascular events, obesity, sarcopenia, osteoporosis, depression,

reduced sexual drive, erectile dysfunction and other chronic diseases

•  Testosterone treatment in Metabolic Syndrome reduces waist circumference, BMI and insulin resistance

•  Young men with TD should also be treated. In older men benefits and risks of testosterone replacement should be carefully assessed

•  Nevertheless, even though these systemic complications, TD is understimated and underthreated

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MMAS (Massachussetts Male Aging Study)

Testosterone levels= good indicator of healthy

Feldman et Al., 2002

Bari 7-10 Novembre Lethality of major cardiovascular events and

testosterone levels

Corona G.et al, J Sex Med 2010;7:1557–1564

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Muraleedharan V et al. Endocrinol Abstracts 2011; 25: 163.

Low testosterone predicts increased mortality and testosterone therapy improves survival in 587

men with type 2 diabetes (mean follow-up: 5.8 years)

Bari 7-10 Novembre Metabolic syndrome and hypogonadism

Muller et Al., 2005

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211 patients screened (mean age 62) •  12 screen failures •  1 AF, 10 raised PSA of which 9 were BPH and 1 new CaP – 1 withdrew consent

199 Randomised •  97 randomised to TESTOSTERONE UNDECANOATE 1000 mg for 30 weeks •  102 randomised to matching placebo for 30 weeks

190 Completed •  4 SAEs – 3 treatment-unrelated deaths and 1 new CaP in PLACEBO arm – 5 withdrawn consent •  106 entered 52-week open-label extension

The BLAST study A 30-week double blind placebo controlled study of long-acting

testosterone undecanoate versus placebo in men with type 2 diabetes

Hackett G et al. J Sex Med 2013

488 consented and attended pre-screening visits

550 men identified from Diabetes register

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HbA1c open-label: Poorly controlled patients (N=45)

Hackett G et al. J Sex Med 2013

Bari 7-10 Novembre HOMA-IR and serum INSULIN levels

Hackett G et al. J Sex Med 2013

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Hackett G et al. J Sex Med 2013

Weight, BMI and waist circumference open-label study (N=106)

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Hackett G et al. J Sex Med 2013

BLAST open-label – IIEF (N=106)

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Hackett G et al. J Sex Med 2013

Variations in total International Prostate Symptom Score (IPSS)

Effects of 5-Year Treatment WithTestosterone Undecanoate on Lower Urinary Tract Symptoms in Obese Men With Hypogonadism and Metabolic Syndrome Davide Francomano, Alessandro Ilacqua, Roberto Bruzziches, Andrea Lenzi, and Antonio Aversa; Urology, 2013 in press

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J Urol 2013;189: S26-S33

Bari 7-10 Novembre IPASS  -­‐  Nebid  

J Sex Med. 2013 Feb;10(2):579-88

•  N=1438 / 1493 patients included in safety population

•  1123 patients completed the study and received

all 5 injections (78.1% continuation rate)

•  In total, 6333 TU injections were administered

•  Mean observation period: 9.2 ± 3.1 months

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Safety data

PSA, prostate-specific antigen; SD, standard deviation

PSA (ng/mL) n Mean SD

Baseline 938 1.10 0.94 Visit 2 708 1.20 1.08 Visit 3 676 1.30 1.18 Visit 4 537 1.20 1.03 Visit 5 455 1.10 1.05

Hematocrit (%) n Mean SD

Baseline 843 42.8 6.56 Visit 2 725 44.0 5.83 Visit 3 684 44.7 6.05 Visit 4 534 44.7 6.18 Visit 5 474 44.5 6.12

Zitzmann M. J Sex Med. 2013 Feb;10(2):579-88

……..nevertheless, even though these systemic complications…… TD is understimated and underthreated! Why? • Understimated: Symptoms and signs of late onset are even milder,

unspecified and difficult to recognize

• Underthreated: fear that testosterone replacement causes -prostate cancer or its progression (in particular in men without severTD) -Polycythemia

→ Long term systemic complications: increment of morbility and mortality

→ Correct diagnosis, clinical assessment and treatment (International Guidelines)

Testosterone Deficiency in Men(TD)/Late Onset Hypogonadism (LOH)

Standard Operating Procedures for Hypogonadism

  SIAMS realised SOPHY (simple and updated diagnostic chart for TD) in order to make easier and promote the diagnosis of testicular deficiency, where is frequent but understimated, as in the practice of diabetologist, internist, cardiologist, endocrinologist, urologist.

  «EDUCATION»

Bari 7-10 Novembre Symptoms of adult vs pre-puberal hypogonadism

*Wu FCW, 2010

Bari 7-10 Novembre Threshold Levels for the Biochemical Diagnosis of TD There are no generally accepted lower limits of normal TT (total testosterone). There is, however, general agreement that: • TT > 12 nmol/L (3.5 ng/mL or 350 ng/dL) does not usually require substitution (EBMI1) • Based on the data of young hypogonadal men, men with TT < 8 nmol/L (2.3 ng/mL or 230 ng/dL) usually benefit from T treatment (EBMI1) • Between these levels: -measuring FT (free testosterone) by equilibrium dialysis or calculating it from TT and SHBG levels* may be helpful in case of TT between 8 and 12 nmol/L. A lower limit of 225 pmol/L (65 pg/mL) is accepted by many (EBMI3) *www.issam.ch/freetesto.htm.

Buvat, 2013

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SOPHY Project

•  In the pilot phase of SOPHY:

5 centers, 47 physicians

•  From December 2013 available on

SIAMS site

Standard Operating Procedures for Hypogonadism

Foggia Mauro Cignarelli

Udine Franco Grimaldi

Milano Luca Persani

Napoli Rosario Pivonello

Roma Rocco Rago

Coordinator: Alessandro Pizzocaro MD

&

Analysis of current situation

Diagnosis of Hypogonadism

128/272

Correct diagnosis of hypogonadism

122/128 95.3%

Previous diagnosis 37/128 New diagnosis 91/128

26 active physicians, 319 filled questionnaires, 272 analyzed

71,20% 28,80%

Exclusion of Hypogonadism

correct diagnosis

wrong diagnosis

Causes of error

Total testosterone Borderline (NO SHBG)

32.5%

NO testosterone assay in presence of symptoms

55%

Other 12.2%

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Exclusion of Hypogonadism: wrong diagnosis Specialist in Diabetology

•  Patient: 71years old, married, 2 sons, with hypertension, diabetes, cardiovascular disease, BPH, BPCO

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Hypogonadism Symptoms

Bari 7-10 Novembre Clinical diagnosis and laboratory analysis

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80,80%

16,5% 7,0%

Hypogonadism Treatment

Treated Not treated Not treated (other Specialist)

Hypogonadism Treatment Percentage in diagnosed cases

Hypogonadism Not TreatedSpecialist in Endocrinology

Altro: Dislipidemia Terapia: Eutirox mcg/die, Omeprazolo mg, Vytorin.

Non valutati: didimi e prostata

•  Patient: 45 years old, married, no sons, familiar with T2 diabetes mellitus and cardiovascular disease; 1 cigar; < 2 drink; no sport

Bari 7-10 Novembre Hypogonadism Symptoms

Diagnosis

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Inj. Long- acting 20,4%

Inj. Short- acting 27,6%

Gel 36,8%

Oral 2%

Not specif. 7,1% Gonadotropin

6,1%

Inj. Long- acting (Nebid)

Inj. Short- acting (Testoenant, Testoviron e Sustanon) Gel (Tostrex, Testogel, Testim)

Oral (Andriol)

Not Specified

Gonadotropin

Formulation

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Thanks for your attention!

Alessandro Pizzocaro